Senile dementia caused by such cerebral disorders as cerebrovascular disorder, cerebral circulation disorder, cerebral metabolism disorder, and memory disturbance has become a social problem in the society with prolonged life-span. A number of drugs for the treatment or prevention of these diseases, including cerebral vasodilators, cerebral metabolism accelerators, and the like, are clinically used.
None of these medicines, however, exhibit sufficient effects on the treatment of diseases such as cerebrovascular disorder sequelae, or the like.
Cerebral tissues of mammals rely upon aerobic glycolysis for the energy to maintain their functional activity. For this reason, a constant supply of a large amount of oxygen and glucose to brain tissues is necessary. It is a clinical knowledge that a decreased oxygen supply to brain tissues caused by circulation disorder, or the like remarkably lowers the brain cell functions. The continued decrease in oxygen supply to brain tissues extremely lowers brain cell functions. Interruption of oxygen supply (for several minutes) is known to completely inactivate physiological functions of brain cells and to cause irreversible organic disorders [J. Cereb. Blood Flow Metab. 9, 2-19, (1989]. In view of this, pharmacological experiments using hypoxia induction methods have long been carried out. A great attention to the problems concerning cerebral ischemia in recent years has led to the investigations about the cause of cerebral functional disorder or cerebral tissue disorder. The studies involving biochemistry, blood circulation dynamics, and electrophysiology resulted in the evidenced utility of hypoxia induction methods [Arch. Int. Pharmacodyn. 286, 299-307 (1987)]. Drugs protecting the brain from the induced hypoxia have been recognized as possessing more excellent effects on the improvement in cerebral circulation and cerebral metabolism, as well as on the prevention of amnesia than conventional drugs for improving cerebral circulation.
In view of this situation, the present inventors have undertaken extensive studies in order to develop a more excellent medicine for improving cerebral circulation and metabolism as well as for preventing amnesia. As a result, the inventors have found that phenylalkanoylamine derivatives represented by the following formula (I) exhibited excellent anti-hypoxic and anti-amnesic activities, and are pharmacologically useful. Such findings have led to the completion of this invention.